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Review
. 2018 Jun;75(11):1947-1957.
doi: 10.1007/s00018-018-2770-7. Epub 2018 Feb 8.

Cellular functions of stem cell factors mediated by the ubiquitin-proteasome system

Jihye Choi  1 , Kwang-Hyun Baek  2
Affiliations
Review

Cellular functions of stem cell factors mediated by the ubiquitin-proteasome system

Jihye Choi et al. Cell Mol Life Sci. 2018 Jun.

Abstract

Stem cells undergo partitioning through mitosis and separate into specific cells of each of the three embryonic germ layers: endoderm, mesoderm, and ectoderm. Pluripotency, reprogramming, and self-renewal are essential elements of embryonic stem cells (ESCs), and it is becoming evident that regulation of protein degradation mediated by the ubiquitin-proteasome system (UPS) is one of the key cellular mechanisms in ESCs. Although the framework of that mechanism may seem simple, it involves complicated proteolytic machinery. The UPS controls cell development, survival, differentiation, lineage commitment, migration, and homing processes. This review is centered on the connection between stem cell factors NANOG, OCT-3/4, SOX2, KLF4, C-MYC, LIN28, FAK, and telomerase and the UPS. Herein, we summarize recent findings and discuss potential UPS mechanisms involved in pluripotency, reprogramming, differentiation, and self-renewal. Interactions between the UPS and stem cell transcription factors can apply to various human diseases which can be treated by generating more efficient iPSCs. Such complexes may permit the design of novel therapeutics and the establishment of biomarkers that may be used in diagnosis and prognosis development. Therefore, the UPS is an important target for stem cell therapeutic product research.

Keywords: Deubiquitinating enzyme; Deubiquitination; E3 ligase; Post-translational modification; Ubiquitination.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Reprogramming somatic cells into iPSCs. Differentiation process of stem cells from somatic cells to iPSCs is regulated by several kinds of reprogramming factors such as NANOG, KLF4, OCT-3/4, SOX2, C-MYC, LIN28, FAK, and telomerase
Fig. 2
Fig. 2
Interaction of the stem cell transcription factors with E3 ligases and DUBs. Various DUBs and E3 ligases regulate stem cell transcription factors including NANOG, KLF4, OCT-3/4, SOX2, C-MYC, LIN28, FAK, and telomerase. By deubiquitination, stem cell transcription factors regulate stem cell maintenance. Contrary to this, stem cell transcription factors regulate stem cell differentiation by ubiquitination
See this image and copyright information in PMC

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